Molecule Stops Fatal Pediatric Brain Tumor

Children under 10 years old are primarily affected

Ali Shilatifard, PhD, chair and Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics, was the senior author of the study that found a potential treatment for diffuse intrinsic pontine glioma.

In research published in Nature Medicine, Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive pediatric brain tumor.

Every year, about 300 children under the age of 10 years old in the U.S. develop the tumor, referred to as diffuse intrinsic pontine glioma (DIPG), which is always fatal.

“This tumor kills every single kid who gets DIPG within one year. No one survives,” said the study’s first author, Andrea Piunti, PhD, a postdoctoral fellow in the lab of Ali Shilatifard, PhD, chair and Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics.

“To the best of our knowledge, this is the most effective molecule so far in treating this tumor,” said senior author Shilatifard. “Every other therapy that has been tried so far has failed.”

No children suffering from DIPG have survived longer than one year. Northwestern scientists believe a new molecule may be able to buck that trend.

Radiation therapy only prolongs patients’ survival by a few months, he noted.

Shilatifard’s lab previously identified the pathway through which a mutation causes this cancer in studies with fruit flies, research published in Science a few years ago.

In a study with Hashizume’s group, they demonstrated that mice that had the drug delivered through their abdomen had an increased survival of 20 days, which is a long time in the life of a mouse, Piunti said. Now the team at Northwestern Medicine and Lurie Children’s is working on delivering the drug to the brain stem to see if the effect will be more potent.

To test the molecule, scientists took tumor cell lines from a pediatric patient who was untreated and injected those cells into the brain stem of a mouse. The human tumor engrafted in the brain of the mouse. The mouse was then treated with the molecule while scientists monitored the tumor. The molecule stopped the growth of the tumor cells and forced them to turn into other types of cells, known as differentiation, thereby halting its growth.

“This discovery is the perfect example of how we take basic science discoveries and translate them to cure diseases at Northwestern Medicine.” – Ali Shilatifard, PhD

This molecule detaches proteins, known as bromodomain proteins, from their binding to a mutant protein, the histone H3K27M, which is present in more than 80 percent of these tumors.

While the molecule itself is not yet available commercially, another similar class of molecules, BET inhibitors, is being tested in clinical trials for pediatric leukemia and other types of tumors. These could be used in a clinical trial for the pediatric tumor, Piunti said.

The collaborative environment at Northwestern made the discovery possible, Shilatifard said.

“This work could not have been done anywhere in the world except Northwestern Medicine, because of all the scientists and physicians who have been recruited here during the past five years and how they work together to link basic scientific research to the clinic,” Shilatifard said. “This discovery is the perfect example of how we take basic science discoveries and translate them to cure diseases at Northwestern Medicine.”

About Author

Marla Paul

Marla Paul is the health sciences editor for Northwestern University Media Relations. She is a veteran journalist, formerly a staff writer at the Chicago Sun-Times, and her writing has appeared in the Chicago Tribune and many national publications.
marla-paul@northwestern.edu
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